We hypothesize that a newly redesigned portable tomographic version of Near Infrared Spectroscopy (NIRS), developed and tested at Dartmouth over the past 15 years, can successfully characterize changes in breast tumor vascularity, and potentially cellular metabolism, more accurately and with higher spatial resolution than other NIRS technologies currently under investigation, and is better suited to clinical oncology workflow. NIRS tomography (NIRST) is a unique tool for characterizing tissue composition in the female breast which generates images of total hemoglobin concentration (HbT), tissue oxygen saturation (StO2), water fraction, as well as elastic scattering parameters. Based on results obtained in previous studies, the overall goal of this proposal is to develop and evaluate a portable and compact NIRST system that is expected to quantify changes in HbT, StO2 and water fraction more accurately as early indicators of treatment response of locally advanced breast cancers receiving neoadjuvant chemotherapy (NAC), and will have additional wavelengths enabling the recovery of new images of lipid and collagen content. Comparisons to results obtained with hand- held Diffuse Optical Spectroscopic Imaging (DOSI), which has undergone a recently-completed national multi- center (ACRIN) trial, will occur. The proposed mobile NIRST system will integrate into the workflow of clinical oncology practice to maximize patient accrual and participation in the proposed studies, assess the presence of a flair response, and determine whether prognostic information can be obtained that would influence patient management. After developing and validating the new portable NIRST platform with phantom and normal- subject studies, we will quantitatively assess our hypothesis by 1) imaging the response of tumor vasculature before, during and after infusions associated with different treatment cycles of NAC, and 2) quantify pathological and clinical outcomes of response to NAC, and relate these outcomes to changes in NIRST properties measured at different time points during NAC. The project will extend successful preliminary results obtained in studies supported through completed NIH P01 (P01-CA80139, PI Paulsen) and R21 (CA135303, PI Jiang) grants. It also leverages the extensive infrastructure we have developed for breast cancer imaging where investigators from medical oncology, surgical pathology and biomedical optical engineering have collaborated to develop and evaluate advanced technology for breast cancer imaging for more than a decade.